| Literature DB >> 19060911 |
Yurii S Aulchenko1, Samuli Ripatti, Ida Lindqvist, Dorret Boomsma, Iris M Heid, Peter P Pramstaller, Brenda W J H Penninx, A Cecile J W Janssens, James F Wilson, Tim Spector, Nicholas G Martin, Nancy L Pedersen, Kirsten Ohm Kyvik, Jaakko Kaprio, Albert Hofman, Nelson B Freimer, Marjo-Riitta Jarvelin, Ulf Gyllensten, Harry Campbell, Igor Rudan, Asa Johansson, Fabio Marroni, Caroline Hayward, Veronique Vitart, Inger Jonasson, Cristian Pattaro, Alan Wright, Nick Hastie, Irene Pichler, Andrew A Hicks, Mario Falchi, Gonneke Willemsen, Jouke-Jan Hottenga, Eco J C de Geus, Grant W Montgomery, John Whitfield, Patrik Magnusson, Juha Saharinen, Markus Perola, Kaisa Silander, Aaron Isaacs, Eric J G Sijbrands, Andre G Uitterlinden, Jacqueline C M Witteman, Ben A Oostra, Paul Elliott, Aimo Ruokonen, Chiara Sabatti, Christian Gieger, Thomas Meitinger, Florian Kronenberg, Angela Döring, H-Erich Wichmann, Johannes H Smit, Mark I McCarthy, Cornelia M van Duijn, Leena Peltonen.
Abstract
Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.Entities:
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Year: 2008 PMID： 19060911 PMCID： PMC2687074 DOI： 10.1038/ng.269
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330